PXD039385

PXD039385 is an original dataset announced via ProteomeXchange.

Title	Piperlongumine (PL) conjugates induce targeted protein degradation
Description	PROteolysis Targeting Chimeras (PROTACs) are bifunctional molecules that degrade target proteins through recruiting E3 ligases. However, their application is limited in part because few E3 ligases can be recruited by known E3 ligase ligands. In this study, we identified piperlongumine (PL), a natural product, as a covalent E3 ligase recruiter, which induces CDK9 degradation when it is conjugated with SNS-032, a CDK9 inhibitor. To evaluate the specificity of the PL-SNS-032 lead conjugate named 955, TMT-based proteomics were conducted to compare 955 with its warhead SNS-032 in MOLT4 cells. As expected, cells exhibited a significant reduction of CDK9 after treatment with 0.1 µM 955 for 1 h and 6 h while treatment with 1 µM SNS-032 for 6 h had no significant effect on CDK9. Interestingly, 955, but not SNS-032, can also potently degrade CDK10.
HostingRepository	PRIDE
AnnounceDate	2024-05-24
AnnouncementXML	Submission_2024-05-24_01:01:56.417.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Dongwen Lyu
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-01-13 05:36:20	ID requested
⏵ 1	2024-05-24 01:01:57	announced

Pei J, Xiao Y, Liu X, Hu W, Sobh A, Yuan Y, Zhou S, Hua N, Mackintosh SG, Zhang X, Basso KB, Kamat M, Yang Q, Licht JD, Zheng G, Zhou D, Lv D, Piperlongumine conjugates induce targeted protein degradation. Cell Chem Biol, 30(2):203-213.e17(2023) [pubmed]

10.1016/j.chembiol.2023.01.004;

submitter keyword: Piperlongumine, PROTAC, E3 ligase, CDK9

Dongwen Lv
contact affiliation	Department of Biochemistry and Structural Biology and Center for Innovative Drug Discovery School of Medicine, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, United States
contact email	lyud@uthscsa.edu
lab head
Dongwen Lyu
contact affiliation	UT Health San Antonio
contact email	lyud@uthscsa.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/05/PXD039385

PRIDE project URI

• PRIDE
  1. PXD039385
     1. Label: PRIDE project
     2. Name: Piperlongumine (PL) conjugates induce targeted protein degradation